ORLANDO, Fla.—In a heavily pretreated population with multiple myeloma, the combination of bendamustine and bortezomib appears to be safe and effective, results of an open-label phase 1 study have found. The phase 2 study is ongoing.

Bendamustine, approved in Europe for the treatment of multiple myeloma and in the United States for chronic lymphocytic leukemia (CLL) and refractory indolent B-cell non-Hodgkin's lymphoma (NHL), is a unique chemotherapeutic agent that combines an alkylating group with a purine-like benzimidazole ring. Bortezomib, a proteasome inhibitor approved for the treatment of multiple myeloma, has proven to be highly effective in combination with melphalan and cyclophosphamide. The combination of lower doses of bortezomib with bendamustine, therefore, may provide additional therapeutic options in patients previously treated with bortezomib while potentially reducing the incidence of peripheral neuropathy.

The phase 1/2 study enrolled patients with multiple myeloma who relapsed after or were refractory to at least 1 previous treatment, according to James R. Berenson, MD, Institute for Myeloma & Bone Cancer Research, West Hollywood, Calif., and colleagues in a poster presentation during the 52nd American Society of Hematology Meeting and Exposition. Each patient received bendamustine over 1 hour on days 1 and 4 in 3-dose cohorts of 50, 70, or 90 mg/m2 and bortezomib on days 1, 4, 8, and 11 at a fixed dose of 1.0 mg/m2 every 28 days for up to 8 cycles. At each dose cohort, 3 patients were initially enrolled; however, up to 5 patients could be enrolled if they were in the screening phase prior to the third patient being enrolled.

After the first 3 patients completed the first cycle of each dose, the cohort was assessed for dose-limiting toxicities (DLTs), defined as study drug-related grade 3/4 non-hematologic toxicity; grade 4 hematologic toxicity; grade 3 thrombocytopenia with grade 3/4 hemorrhage; grade 3 febrile neutropenia; grade 3/4 nausea and vomiting refractory to antiemetic therapy; or any drug-related deaths. The maximum tolerated dose (MTD) was determined using a standard 3+3 approach; this cohort was then expanded to enroll up to 40 patients.

To date, 25 patients have received at least 1 dose of study drug. Median age is 62 years (range, 44-91 years); 52% are male; and 80% had received at least one prior regimen containing bortezomib (median 4 regimens; range, 1-17). Five patients were enrolled in the 50 mg/m2 cohort, 4 in the 70 mg/m2 cohort, and 5 in the 90 mg/m2 cohort. No DLTs were observed. The MTD of bendamustine, 90 mg/m2, was well tolerated and is the dose patients are receiving in combination with bortezomib in the ongoing phase 2 portion of the study. Of the 25 patients, 8 achieved a molecular or partial response.